2021 Fiscal Year Final Research Report
Analysis of airway mucociliary transport via Toll-like receptors pathway
| Project/Area Number |
19K08600
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
鈴木 哲朗 浜松医科大学, 医学部, 教授 (00250184)
須田 隆文 浜松医科大学, 医学部, 教授 (30291397)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 線毛輸送系 / ウイルス感染 / 線毛運動 / Toll-like receptor / 生体防御 / 長時間作用性抗コリン薬 |
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| Outline of Final Research Achievements |
Mucociliary clearance is an airway defense mechanism that removes pathogens from the respiratory tract. However, the impact of innate immune response on mucociliary clearance remains unclear. To elucidate the mechanism of TLR-mediated promotion of mucociliary clearance, we focused on the TLR3 pathway and evaluated the effects of polyI:C and influenza A virus (IAV) infection on the promotion of ciliary activity and cilia-driven flow using murine tracheal tissue culture model. We found that polyI:C and IAV infection readily increased ciliary activity and cilia-driven flow via TLR3 activation. Mechanically, extracellular ATP release in response to TLR3 activation promotes ciliary activity through autocrine ATP-P2R loop.
We also analyzed the effects of long-acting muscarinic antagonists (LAMAs), therapeutics for asthma and COPD, on ciliary activity and cilia-driven flow. We found that the LAMAs, tiotropium and glycopyrronium, exerted a direct effect to enhance airway ciliary function.
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| Free Research Field |
呼吸器内科学
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究により，IAV感染において、気道上皮は線毛輸送系を促進して、気道の生体防御に寄与することが明らかとなった．この結果は，IAVだけでなくRNAウイルス全般（コロナウイルス，ライノウイルスなど），ひいては現在猛威を振うCOVID-19に対する気道の生体防御機構の解明に応用できる．さらに，メカニズムを詳細に解明することにより，線毛輸送系の促進をターゲットにした新たな創薬研究に発展させることが可能となる．
また，既存の治療薬であるLAMAの新規作用として，線毛機能促進作用を明らかにしたことは，慢性気道疾患における生体防御の観点から臨床的な意義は大きい．
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